Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos. (1/575)

Experiments were conducted to survey and detect differences in plasma corticosterone concentrations and intermediary metabolic enzyme activities in herring gull (Larus argentatus) embryos environmentally exposed to organochlorine contaminants in ovo. Unincubated fertile herring gull eggs were collected from an Atlantic coast control site and various Great Lakes sites in 1997 and artificially incubated in the laboratory. Liver and/or kidney tissues from approximately half of the late-stage embryos were analyzed for the activities of various intermediary metabolic enzymes known to be regulated, at least in part, by corticosteroids. Basal plasma corticosterone concentrations were determined for the remaining embryos. Yolk sacs were collected from each embryo and a subset was analyzed for organochlorine contaminants. Regression analysis of individual yolk sac organochlorine residue concentrations, or 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs), with individual basal plasma corticosterone concentrations indicated statistically significant inverse relationships for polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs), total polychlorinated biphenyls (PCBs), non-ortho PCBs, and TEQs. Similarly, inverse relationships were observed for the activities of two intermediary metabolic enzymes (phosphoenolpyruvate carboxykinase and malic enzyme) when regressed against PCDDs/PCDFs. Overall, these data suggest that current levels of organochlorine contamination may be affecting the hypothalamo-pituitary-adrenal axis and associated intermediary metabolic pathways in environmentally exposed herring gull embryos in the Great Lakes.  (+info)

Effects of dioxins on human health: a review. (2/575)

The toxicity of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) has been known since 1950s. TCDD is a by-product of herbicide 2,4-dichloroacetophenol (2,4-D) and 2,4,5-trichloroacetophenol (2,4,5-T), but it was first found in fryash of municipal incinerator in 1979 in Japan. In 1998, the survey of municipal incinerators revealed that 105 out of 1,641 produced above the allowed emission level of 80 ng TEQ/m3. Total annual release of dioxins is estimated to be about 5,000 g TEQ in 1997 in Japan. Japanese government started a comprehensive survey for dioxin levels in milk and blood of residents around incinerators, and their health effects. Human effects by dioxin exposures in Western countries were mostly acute and at high level in accidentally and/or occupationally. Health effects of low-dose and long lasting exposure has not been well understood. Certain amount of polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) is accumulated in our body. Mother's milk is also contaminated by PCDD/PCDF. Health effects of the polychlorinated chemicals are summarized, and the necessity of regulations and recommendations for making a guideline is discussed in this review.  (+info)

Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. Demonstration of competition and compensation. (3/575)

The aryl hydrocarbon receptor (AHR) and the alpha-class hypoxia inducible factors (HIF1alpha, HIF2alpha, and HIF3alpha) are basic helix-loop-helix PAS (bHLH-PAS) proteins that heterodimerize with ARNT. In response to 2,3,7,8-tetrachlorodibenzo-p-dioxin, the AHR. ARNT complex binds to "dioxin responsive enhancers" (DREs) and activates genes involved in the metabolism of xenobiotics, e.g. cytochrome P4501A1 (Cyp1a1). The HIF1alpha.ARNT complex binds to "hypoxia responsive enhancers" and activates the transcription of genes that regulate adaptation to low oxygen, e.g. erythropoietin (Epo). We postulated that activation of one pathway would inhibit the other due to competition for ARNT or other limiting cellular factors. Using pathway specific reporters in transient transfection assays, we observed that DRE driven transcription was markedly inhibited by hypoxia and that hypoxia responsive enhancer driven transcription was inhibited by AHR agonists. When we attempted to support this cross-talk model using endogenous loci, we observed that activation of the hypoxia pathway inhibited Cyp1a1 up-regulation, but that activation of the AHR actually enhanced the induction of Epo by hypoxia. To explain this unexpected additivity, we examined the Epo gene and found that its promoter harbors DREs immediately upstream of its transcriptional start site. These experiments outline conditions where inhibitory and additive cross-talk occur between the hypoxia and dioxin signal transduction pathways and identify Epo as an AHR-regulated gene.  (+info)

Removal of dibenzofuran, dibenzo-p-dioxin, and 2-chlorodibenzo-p-dioxin from soils inoculated with Sphingomonas sp. strain RW1. (4/575)

Removal of dibenzofuran, dibenzo-p-dioxin, and 2-chlorodibenzo-p-dioxin (2-CDD) (10 ppm each) from soil microcosms to final concentrations in the parts-per-billion range was affected by the addition of Sphingomonas sp. strain RW1. Rates and extents of removal were influenced by the density of RW1 organisms. For 2-CDD, the rate of removal was dependent on the content of soil organic matter (SOM), with half-life values ranging from 5.8 h (0% SOM) to 26.3 h (5.5% SOM).  (+info)

Repression of dioxin signal transduction in fibroblasts. Identification Of a putative repressor associated with Arnt. (5/575)

Heterodimeric complexes of basic helix-loop-helix/PAS transcription factors are involved in regulation of diverse physiological phenomena such as circadian rhythms, reaction to low oxygen tension, and detoxification. In fibroblasts, the basic helix-loop-helix/PAS heterodimer consisting of the ligand-inducible dioxin receptor and Arnt shows DNA-binding activity, and the receptor and Arnt are able to activate transcription when fused to a heterologous DNA-binding domain. However, fibroblasts are nonresponsive to dioxin with regard to induction mediated by the DNA response element recognized by the receptor and Arnt. Here we demonstrate that Arnt is associated with a fibroblast-specific factor, forming a complex that is capable of binding the dioxin response element. This factor may function as a repressor since negative regulation of target gene induction appears to be abolished by inhibition of histone deacetylase activity by trichostatin A. Finally, the negative regulatory function of this factor appears to be restricted for dioxin signaling since Arnt was able to mediate, together with hypoxia-inducible factor-1alpha, transcriptional activation in hypoxic cells. Taken together, these data suggest that fibroblast-specific inhibition of dioxin responsiveness involves recruitment by Arnt of a cell type- and signaling pathway-specific corepressor associated with a histone deacetylase.  (+info)

Aromatic hydrocarbon nuclear translocator as a common component for the hypoxia- and dioxin-induced gene expression. (6/575)

Aromatic hydrocarbon nuclear translocator (Arnt) is an ubiquitously expressed protein that contains basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs. Other bHLH-PAS proteins, hypoxia-inducible factor-1alpha (HIF-1alpha) and aromatic hydrocarbon receptor (AhR) mediate hypoxia- and dioxin-signal pathway, respectively. Arnt has been identified as a heterodimerization partner for AhR. AhR/Arnt heterodimer binds the regulatory region of xenobiotic-induced genes and activates their transcription. Here, in vivo results provide evidence that Arnt is involved in not only xenobiotic- but also hypoxia-induced transcriptional activation. In hypoxic condition, Arnt dimerizes with HIF-1alpha to make HIF-1alpha/Arnt heterodimer which is able to bind hypoxia-responsive DNA elements. The HIF-1alpha/Arnt heterodimer functions as a transactivator for hypoxia-inducible genes. Given that the expression of Arnt is limited, HIF-1alpha may compete with AhR for recruiting Arnt as a heteromeric partner. Consistent with this idea, the results indicate that the hypoxic activation of HIF-1alpha reduces dioxin-induced AhR's function on the dioxin-responsive reporter gene and the endogenous gene.  (+info)

A functional 4-hydroxysalicylate/hydroxyquinol degradative pathway gene cluster is linked to the initial dibenzo-p-dioxin pathway genes in Sphingomonas sp. strain RW1. (7/575)

The bacterium Sphingomonas sp. strain RW1 is able to use dibenzo-p-dioxin, dibenzofuran, and several hydroxylated derivatives as sole sources of carbon and energy. We have determined and analyzed the nucleic acid sequence of a 9,997-bp HindIII fragment downstream of cistrons dxnA1A2, which encode the dioxygenase component of the initial dioxygenase system of the corresponding catabolic pathways. This fragment contains 10 colinear open reading frames (ORFs), apparently organized in one compact operon. The enzymatic activities of some proteins encoded by these genes were analyzed in the strain RW1 and, after hyperexpression, in Escherichia coli. The first three ORFs of the locus, designated dxnC, ORF2, and fdx3, specify a protein with a low homology to bacterial siderophore receptors, a polypeptide representing no significant homology to known proteins, and a putative ferredoxin, respectively. dxnD encodes a 69-kDa phenol monooxygenase-like protein with activity for the turnover of 4-hydroxysalicylate, and dxnE codes for a 37-kDa protein whose sequence and activity are similar to those of known maleylacetate reductases. The following gene, dxnF, encodes a 33-kDa intradiol dioxygenase which efficiently cleaves hydroxyquinol, yielding maleylacetate, the ketoform of 3-hydroxy-cis,cis-muconate. The heteromeric protein encoded by dxnGH is a 3-oxoadipate succinyl coenzyme A (succinyl-CoA) transferase, whereas dxnI specifies a protein exhibiting marked homology to acetyl-CoA acetyltransferases (thiolases). The last ORF of the sequenced fragment codes for a putative transposase. DxnD, DxnF, DxnE, DxnGH, and DxnI (the activities of most of them have also been detected in strain RW1) thus form a complete 4-hydroxysalicylate/hydroxyquinol degradative pathway. A route for the mineralization of the growth substrates 3-hydroxydibenzofuran and 2-hydroxydibenzo-p-dioxin in Sphingomonas sp. strain RW1 thus suggests itself.  (+info)

Chlorella accelerates dioxin excretion in rats. (8/575)

We investigated the effects of Chlorella on fecal excretion of polychlorinated dibenzo-p-dioxin (PCDD) congeners and polychlorinated dibenzofuran (PCDF) congeners in Wistar rats administered the rice oil that caused Yusho disease, as a substitute for purified dioxin. The rats were fed 4 g of a control diet or a 10% Chlorella diet containing 0.2 mL of the rice oil once during the 5-d experimental period. The amounts of PCDD and PCDF congeners excreted in feces from d 1 to 5 in the group fed 10% Chlorella were 0.2-11.3 and 0.3-12.8 times greater (P < 0.05), respectively, than those of the control group. We then investigated the fecal excretion of PCDD and PCDF congeners from d 8 to 35 in rats administered 0.5 mL of the rice oil. Rats consumed the basal diet for 1 wk. After 1 wk, they consumed either the basal diet or the 10% Chorella diet. The fecal excretions of PCDD and PCDF congeners in the group fed 10% Chlorella were 0.3-3.4 and 0.5-2.5 times greater (most, P < 0.05), respectively, than those of the control group. Thus, the fecal excretions of PCDD and PCDF congeners were greater in rats fed Chlorella. These findings suggest that the administration of Chlorella may be useful in preventing gastrointestinal absorption and for promoting the excretion of dioxin already absorbed into tissues. Moreover, these findings suggest that Chlorella might be useful in the treatment of humans exposed to dioxin.  (+info)